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    Kratom syrup shows antidepressant effects similar to fluoxetine, suggesting its potential as an alternative therapy. This study used an AI model to analyze brain signals, identifying Kratom syrup as the most promising candidate for depression treatment.

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    Area of Science:

    • Neuroscience
    • Pharmacology
    • Artificial Intelligence

    Background:

    • Kratom (KT) is known for antidepressant (AD) effects, but identifying the most effective form for AD therapy comparable to fluoxetine (flu) is challenging.
    • Evaluating the neurophysiological similarities between different Kratom extracts and standard ADs is crucial for therapeutic development.

    Purpose of the Study:

    • To quantitatively assess the similarity of brain activity patterns induced by various Kratom extracts and fluoxetine using an AI-driven approach.
    • To determine which Kratom formulation exhibits AD properties most comparable to fluoxetine.
    • To evaluate the efficacy of a novel AI model (ANet) in discriminating complex neurophysiological responses.

    Main Methods:

    • Utilized an autoencoder (AE)-based anomaly detector (ANet) to analyze local field potential (LFP) features in mice.
    • Measured the similarity between LFP responses to different Kratom extracts (syrup, alkaloids, aqueous) and fluoxetine.
    • Employed ANet as a multi-task AE for simultaneous classification of LFP responses from various treatments.
    • Visualized learned latent features using t-SNE projection and quantified differences with maximum mean discrepancy.

    Main Results:

    • Kratom syrup extracts demonstrated the highest similarity (87.11 ± 0.25%) to fluoxetine's effects on LFP features.
    • ANet achieved high accuracy (90.11 ± 0.11%) and F1-score (90.08 ± 0.00%) in classifying multi-class LFP responses.
    • Kratom syrup emerged as a more feasible alternative for depression therapy compared to KT alkaloids and aqueous extracts.

    Conclusions:

    • Kratom syrup exhibits significant neurophysiological similarity to the antidepressant fluoxetine, supporting its potential as an alternative therapeutic agent.
    • The developed AI model (ANet) is effective for evaluating the pharmacological profiles of substances like Kratom for therapeutic applications.
    • This research provides a foundation for developing AI-assisted devices for assessing alternative substance profiles, including Kratom-based therapies.